Treatment of primary immune‐mediated hemolytic anemia with mycophenolate mofetil in two cats

Objective – To describe the use of oral mycophenolate mofetil (MMF) as an adjunctive therapy in 2 cats with primary immune‐mediated hemolytic anemia. Case Series Summary – Two cats suffering from presumptive primary immune mediated hemolytic were treated with MMF as part of their treatment regimens. Both cats had improved complete blood counts following therapy. New or Unique Information Provided – This is the first reported use of oral MMF as adjunctive treatment for cats with immune‐mediated hemolytic anemia. Outcome was favorable in both cats and no adverse effects were noted from the MMF.     

Heinz body hemolytic anemia associated with high plasma zinc concentration in a dog

Acute zinc toxicosis from the ingestion of pennies was diagnosed in a dog with Heinz body hemolytic anemia (PCV = 14%), leukocytosis (51,000 cells/ml) with a left shift (3,060 band neutrophils; 37,740 segmented neutrophils) and monocytosis (4,080 cells/ml), azotemia (BUN = 60 mg/dl), bilirubinemia (total bilirubin = 5.3 mg/dl), hypokalemia (3.0 mEq/L), high serum alkaline phosphatase activity (691 U/L), high total plasma solids (8.1 g/dl), hemoglobinuria, and proteinuria. Despite aggressive medical treatment, renal failure ensued, and the dog died of cardiac arrest. The clinical signs, clinical course, and laboratory findings in this dog were similar to what has been reported in other cases of acute zinc toxicosis in dogs, with the exception of a history of generalized seizures and the findings of Heinz bodies. Although a causative relationship between plasma zinc values and Heinz body formation cannot be proven, their association suggests that oxidative damage to erythrocyte hemoglobin and cell membrane proteins may be involved in the pathogenesis of zinc-induced hemolysis.     

Contribution of propylene glycol-induced Heinz body formation to anemia in cats

Propylene glycol (PG) is a common preservative and source of synthetic carbohydrates in soft-moist pet foods. Propylene glycol was fed to cats for 5 weeks at concentrations found in commercial diets (1.6 g/kg of body weight; 12% of diet on a dry-weight basis) and for 3 weeks at concentrations exceeding usual intake (8 g/kg; 41% of diet). There was a dose-dependent increase in Heinz body percentage to 28% in cats fed the low dose of PG and to 92% in cats fed the high dose. Erythrocyte half-life, measured using [14C]-cyanate hemoglobin (Hb), decreased significantly (P less than 0.05) by 18.8% and 60% in cats fed the low and high PG doses, respectively. The PCV in cats fed the low dose was unaffected, whereas cats fed the high dose had a mean (+/- SEM) decrease in PCV from 33.5 +/- 1.05% to 26.3 +/- 1.45%, accompanied by punctate reticulocytosis and bone marrow erythroid hyperplasia. A dose-dependent increase in iron pigment was found in the liver and spleen of all cats. In cats fed the low dose of PG, erythrocyte reduced glutathione concentration actually increased from 7.02 +/- 0.56 to 9.74 +/- 0.69 mumol/g of Hb, but decreased to 2.96 +/- 0.27 mumol/g of Hb in cats fed the high dose. There was no significant increase in methemoglobin concentration. These results indicated that PG cannot be considered innocuous even at concentrations consumed by cats eating commercial diets. Heinz body-induced acceleration of RBC destruction develops in a dose-dependent manner, so that cats with greater food intake, ie, lactating queens and nursing kittens, are at greater risk for development of PG-induced Heinz body hemolytic anemia.     

Propylthiouracil-associated hemolytic anemia, thrombocytopenia, and antinuclear antibodies in cats with hyperthyroidism

Nine of 105 cats with hyperthyroidism treated with propylthiouracil developed a serious immune-mediated drug reaction during treatment. Adverse clinical signs, which developed after 19 to 37 days (mean, 24.8 days) of propylthiouracil administration, included lethargy, weakness, anorexia, and bleeding diathesis. Physical examination revealed pale mucous membranes, and petechial hemorrhages of the skin and oral cavity. Results of hematologic testing revealed severe anemia and thrombocytopenia. The direct antiglobulin (Coombs') test was positive in all 7 cats evaluated, whereas the serum antinuclear antibody titer was greater than or equal to 1:10 in 5 of the 8 cats tested. In 4 of the cats, treatment included appropriate supportive therapy and cessation of propylthiouracil; in these cats, anemia and thrombocytopenia resolved and Coombs' and antinuclear antibody tests became negative within 2 weeks.     

Primary immune-mediated hemolytic anemia in 19 cats: diagnosis, therapy, and outcome (1998-2004)

Immune-mediated hemolytic anemia (IMHA) occurs less frequently in cats than in dogs. The value of the Coombs' test (CT) has been questioned, but detailed surveys of its use are lacking. The objective of this study was to describe 19 cats with primary IMHA (pIMHA) and to examine the diagnostic value of the direct CT. The CT was performed in 92 cats; it was negative in 5 healthy, in 9 sick nonanemic, and in 55 cats with different types of anemia. The CT was positive in 18 anemic cats (2 feline leukemia virus (FeLV) positive, 1 with cholangiohepatitis, 15 with no underlying disease). Moreover, agglutination persisted after saline washing in 5 anemic cats (1 lymphoma, 4 pIMHA). Inclusion criteria for pIMHA were a positive CT (15) or persistent agglutination (4), and the exclusion of other diseases. The age of the 19 cats ranged from 0.5 to 9 years (median, 2 years); male cats were overrepresented. The PCV on admission was 6-22% (median, 12%). The anemia was nonregenerative in 11 cats. Additional abnormal laboratory results were leukocytosis (2), lymphocytosis (6), hyperbilirubinemia (13), hyperglobulimemia (10), and increased liver enzyme activities (10). Initial treatment consisted of blood transfusions (10), crystalloids (11), prednisolone (19), antibiotics (19), and H2-blockers (11). Four of 17 cats were euthanized 9, 63, 240 and 2,160 days after initial presentation (mortality rate, 23.5%). Relapses were reported in 5 of 16 cases (31%). Thus, pIMHA appears to occur more frequently than recognized previously, with a more favorable prognosis in cats than in dogs. The CT was useful in identifying immune-mediated pathogenesis.     

Presumed immune‐mediated hemolytic anemia in two foals with Rhodococcus equi infection

Objective – To describe the clinical presentation, case management, and outcome in 2 foals with Rhodococcus equi infection associated with presumptive severe immune‐mediated hemolytic anemia. Series Summary – Two foals diagnosed with R. equi pneumonia on the basis of tracheal wash cultures, thoracic radiographs, and thoracic ultrasonography were concurrently diagnosed with hemolytic anemia. Both foals required whole blood transfusions, and were treated with the antimicrobial combination of rifampin and a macrolide (eg, clarithromycin, erythromycin, or azithromycin). Dexamethasone was used to prevent further hemolysis in both foals, and to treat acute lung injury/acute respiratory distress syndrome in 1 of the foals. Both foals survived, and required prolonged antimicrobial therapy. New or Unique Information Provided – Although extra‐pulmonary disorders are commonly diagnosed in foals infected with R. equi, hemolytic anemia is rarely described. Dexamethasone is considered the treatment of choice for immune‐mediated hemolytic anemia, but may be contra‐indicated in foals with severe bacterial infections. In these foals, a relatively low dose and short duration of dexamethasone was utilized in an attempt to minimize immune suppression, although early discontinuation in 1 foal precipitated a second hemolytic crisis.     

ACVIM consensus statement on the diagnosis of immune‐mediated hemolytic anemia in dogs and cats

Immune‐mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune‐mediated erythrocyte destruction, and adverse consequences of long‐term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence‐based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors.     

The effects of body weight,body condition score,sex, and age on serum fructosamine concentrations in clinically healthy cats

Background: Serum fructosamine (SF) concentrations depend on plasma glucose concentrations and are used to evaluate glycemic control in animals with diabetes mellitus (DM). Despite the strong association between obesity and DM, the effects of body weight (BW) and body condition on SF concentrations in clinically healthy cats have not been reported. Objective: The aim of the study was to evaluate the effects of BW, body condition score (BCS), sex, and age on SF concentrations in healthy cats. Methods: BW, BCS, and SF concentrations were determined in 84 clinically healthy client‐owned cats (50 neutered males, 33 spayed females, and 1 intact female) of known age. The cats were enrolled prospectively in the study. Results: Mean BW, median BCS, and mean SF concentrations for the 84 cats were 5.4 kg, 5/9, and 268.7±45.5 μmol/L (range 197–399), respectively. BW was weakly but significantly correlated with SF (r=.26; P=.02), whereas BCS was not. Cats weighing >5.4 kg and cats with BCS>5/9 had higher mean SF concentrations compared with cats weighing <5.4 kg and cats with BCS <5/9, respectively. Cats categorized as normal weight to obese by BW (BW≥4.0 kg) had higher mean SF concentrations compared with cats categorized as lean (BW<4.0 kg). For domestic shorthair cats, the same was true for BCS: cats with BCS≥4/9 had higher mean fructosamine concentrations than those with BCS<4/9. Male cats had significantly higher mean SF concentrations compared with female cats (285.1±45.3 vs 244.5±33.9 μmol/L, P<.001). Age did not affect mean SF concentrations. Conclusions: BW is positively correlated with SF concentration, and lean cats have lower SF concentrations than normal and obese cats. In contrast to previous reports, mean SF concentrations were higher in male cats than in female cats, even when males and females were matched based on BW, BCS, and age.     

Assessment of the red blood cell proteome in a dog with unexplained hemolytic anemia

A 7‐year‐old female neutered Jack Russell Terrier was presented to Langford Vets, the University of Bristol, with a history of chronic intermittent lethargy. Investigations and clinical course were compatible with hereditary hemolysis due to a red blood cell membrane defect. Proteomics was used to explore protein alterations in the presence of a hypothesized red blood cell membrane protein deficiency. Proteomic analysis revealed downregulation of the band 3, and alpha‐ and beta‐adducin proteins, and alterations in the red blood cell proteome consistent with previous reports of changes due to the presence of reticulocytosis and ongoing hemolysis. The spectrum of protein alterations identified in the affected dog may be homologous to a band 3 protein deficiency secondary to hereditary spherocytosis, as described in people.     

Use of therapeutic plasmapheresis in a case of canine immune-mediated hemolytic anemia

Objective – To investigate the clinical application and potential utility of plasmapheresis in canine immune-mediated hemolytic anemia.
Case Summary – A 7-year-old spayed female Maltese diagnosed with immune-mediated hemolytic anemia was initially treated with prednisone, cyclosporine, and received multiple transfusions of packed RBC. Because of the progression of clinical signs despite traditional medical therapy, plasmapheresis was initiated. Plasma immunoglobulin G and immunoglobulin M levels were measured before, during, and after treatment to help determine if there had been a significant decrease in immunoglobulin levels with plasmapheresis. Plasmapheresis was successfully performed over a 2.5-hour period in this dog with minimal complications. Hypocalcemia was identified as a known complication of circuit anticoagulation, and was corrected through calcium supplementation. Post-plasmapheresis there was a decrease in immunoglobulin G and immunoglobulin M levels, and the patient showed clinical improvement. Following discharge the dog had no known complications of therapy, and had complete resolution of the anemia.
New or Unique Information Provided – Plasmapheresis was performed successfully with minimal complications. Because transfusion requirements appeared to be reduced, and the procedure was well tolerated, there may be a place for this modality in severe cases to act as a bridge until medical therapy takes full effect. Because of the cost of performing this therapy, and the potential requirement for multiple treatments, it should be reserved for selected patients.     

Heinz body anemia in a dog that had been sprayed with skunk musk

A 5-year-old pit bull-type dog was examined because of lethargy and black feces, and a presumptive diagnosis of methemoglobinemia was made on the basis of grossly visible brown discoloration of the mucous membranes and urine. Heinz body formation was seen on examination of blood smears, and severe anemia developed 3 days later. The dog did not have any history of exposure to toxins or drugs that have been associated with Heinz body formation. The only remarkable historical finding was that the dog had been wandering loose the day prior to initial examination and returned home smelling strongly of skunk spray. Skunk spray contains thiols and other compounds that are strong oxidizing agents. It was speculated that the methemoglobinemia and Heinz body anemia were a result of exposure to these compounds. Skunk interactions with dogs usually have malodorous but otherwise harmless results. However, findings in this dog suggest that more serious consequences may develop in isolated cases.